Ethyl bromoacetate → 2-[3-(1-Adamantyl)-4-benzyloxyphenyl]-5-(carbethoxymethylamino)pyrimidine

HRID 508655ノート

反応式

HRID 508655 の反応式
[NH2:1][C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:10]([C:22]34[CH2:31][CH:26]5[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]5)[CH2:23]3)[CH2:29]4)[CH:9]=2)=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41]>CC(C)=O>[C:22]12([C:10]3[CH:9]=[C:8]([C:5]4[N:6]=[CH:7][C:2]([NH:1][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:3][N:4]=4)[CH:13]=[CH:12][C:11]=3[O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:23][CH:24]3[CH2:30][CH:28]([CH2:27][CH:26]([CH2:25]3)[CH2:31]1)[CH2:29]2

参加物

5

反応物 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 532600875-Amino-2-[3-(1-adamantyl)-4-benzyloxyphenyl]pyrimidine

生成物 1

HCID 532602482-[3-(1-Adamantyl)-4-benzyloxyphenyl]-5-(carbethoxymethylamino)pyrimidine収率 89%

試薬・触媒・溶媒 1

HCID 180Acetone溶媒

実験手順

To a suspension of 5-amino-2-[3-(1-adamantyl)-4-benzyloxyphenyl]pyrimidine (49 mg, 0.12 mmol) and K2CO3 (69 mg, 0.50 mmol) in acetone (5 mL) was added ethyl bromoacetate (53 μl, 0.48 mmol). The mixture was heated at reflux under argon for 19 h and cooled to room temperature. After removal of acetone at reduced pressure, the residue was diluted with water (8 mL) and extracted with EtOAc (60 mL). The extract was washed (H2O and brine) and dried. After solvent removal at reduced pressure, the residue was chromatographed (14% EtOAc/hexane) to give 53 mg (89%) of 2-[3-(1-adamantyl)-4-benzyloxyphenyl]-5-(carbethoxymethylamino)pyrimidine as a pale-tan solid, mp 153-156° C. IR 3455, 2901, 1710, 1179 cm−1; 1H NMR (CDCl3) δ 1.33 (t, J=7.2 Hz, 3H, OCH2CH3), 1.75 (bs, 6H, AdCH2), 2.07 (bs, 3H, AdCH), 2.24 (m, 6H, AdCH2), 4.31 (q, J=7.2 Hz, 2H, OCH2CH3), 4.60 (m, 1H, NH), 4.73 (s, 2H, NHCH2CO), 5.20 (s, 2H, C6H5CH2), 7.03 (d, J=8.4 Hz, 1H, 5′-ArH), 7.32-7.55 (m, 5H, C6H5), 8.17 (dd, J=8.4 Hz, 2.1 Hz, 1H, 6′-ArH), 8.32 (d, J=2.1 Hz, 1H, 2′-ArH), 8.46 ppm (s, 2H, 4-ArH, 6-ArH). HRMS calcd C31H35N3O3 [M+H]+ 498.2757. found 498.2762.

後処理

  1. temperatureThe mixture was heated
  2. temperatureat reflux under argon for 19 h
  3. customAfter removal of acetone at reduced pressure
  4. additionthe residue was diluted with water (8 mL)
  5. extractionextracted with EtOAc (60 mL)
  6. washThe extract was washed (H2O and brine)
  7. customdried
  8. customAfter solvent removal at reduced pressure
  9. customthe residue was chromatographed (14% EtOAc/hexane)

出典と根拠

ORDレコード
ord-f6df03d07f164490ae387828e35e93f9
出典データセット
uspto-grants-2015_08
特許番号
US09096544B2

反応ノート

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